Cellular and Molecular NeuroscienceResearch PaperNonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro
Highlights
▶Mefloquine did not affect ripple oscillations during hippocampal sharp wave-ripples. ▶Mefloquine reduced ripple amplitude during epileptiform discharges. ▶Mefloquine increased afterhyperpolarization following evoked APs and reduced neuronal excitability in CA3 pyramidal cells.
Section snippets
Slice preparation
Animal procedures were performed in accordance with the guidelines of the European Communities Council and approved by the regional authority (LaGeSO Berlin: T0068/02). Wistar rats (aged 6–8 weeks, ∼200 g) of either sex were decapitated under deep ether anesthesia. Horizontal hippocampal slices (400 μm/at bregma −4.7 to −7.3 mm) were prepared at an angle of ∼12 degree in the fronto–occipital direction (with the frontal portion up) using a vibratome (752 M Vibroslice, Campden Instruments,
Effects of mefloquine on sharp wave-ripple complexes
In order to test for effects of mefloquine on SPW-Rs, we induced such events by recurrent high frequency stimulation (HFS) applied to stratum radiatum (SR) in the proximal CA1 region, which induced two population spikes (PSs) in area CA3. During such stimulation the first PS is due to antidromic propagation of APs along CA3 axon fibers (Schaffer collaterals), and the second is due to generation of excitatory postsynaptic potentials (EPSPs) generated by recurrent axon collaterals within area CA3
Discussion
Our findings indicate that mefloquine significantly reduced ripple oscillations during REDs, which were recorded in the absence of GABAergic transmission while ripple oscillations during SPW-Rs were not significantly changed. In CA3 pyramidal cells, 50 μM mefloquine caused a reduction in AP firing during positive current-injection and significantly increased the amplitude of the AHP following APs while neither the resting membrane potential nor the input resistance was changed. Finally, the
Conclusion
Based on our data, we cannot exclude that synchronization during REDs might partly be mediated by Cx36-gap junctions but the present data rather indicate that mefloquine is not specific enough to prove that point.
Acknowledgments
We are grateful to Drs. H. J. Gabriel and H. Siegmund for excellent technical support and development of data analysis tools. This research was supported by the Excellence cluster NeuroCure, by DFG grant he 1173/17-1, GRK 1123 “Cellular mechanisms of learning and memory consolidation” and by a grant from the Hertie Foundation. RuH is a recipient of a grant from the DAAD and the HEC of Pakistan.
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